Defining the underlying pathology of corticobasal syndrome using clinical features and biomarkers.
Defining the underlying pathology of corticobasal syndrome using clinical features and biomarkers.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
London, GB · Author affiliation
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.Location evidence
Cambridge, GB · Author affiliation
Department of Clinical Neurosciences, University of Cambridge and Cambridge University Hospitals NHS Trust, CB2 OSZ, UK.Location evidence
Birmingham, GB · Author affiliation
Department of Biomedical Sciences, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham, B15 2TT, UK.Location evidence
Catanzaro, IT · Author affiliation
Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy.Location evidence
Gothenburg, SE · Author affiliation
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal 405 30, Sweden.Location evidence
Mölndal, SE · Author affiliation
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal 405 30, Sweden.Location evidence
US · Author affiliation · country only
Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.Location evidence
IN · Author affiliation · country only
Centre for Brain Research, Indian Institute of Science, Bangalore 560012, India.Location evidence
Dublin, IE · Author affiliation
Department of Neurology, Dublin Neurological Institute at the Mater Misericordiae University Hospital and Health Affairs and School of Medicine University College Dublin Ireland, Dublin, D07 W7XF, Ireland.Location evidence
Sevilla, ES · Author affiliation
Unidad de Trastornos del Movimiento, Servicio de Neurología, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41004 Seville, Spain.Location evidence
Universidad, ES · Author affiliation
Unidad de Trastornos del Movimiento, Servicio de Neurología, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41004 Seville, Spain.Location evidence
Centro, ES · Author affiliation
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid 28029, Spain.Location evidence
Madrid, ES · Author affiliation
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid 28029, Spain.Location evidence
Athens, GR · Author affiliation
Parkinson's disease and Movement Disorders Department, HYGEIA Hospital, Athens 151 23, Greece.Location evidence
Innsbruck, AT · Author affiliation
Department of Neurology, Medical University Innsbruck, A-6020 Innsbruck, Austria.Location evidence
Leuven, BE · Author affiliation
Laboratory for Cognitive Neurology, Department of Neurosciences, University of Leuven, Leuven 3001, Belgium.Location evidence
GB · Author affiliation · country only
Department of Neurology, Royal Gwent Hospital, Newport, NP20 2UB, UK.Location evidence
Manchester, GB · Author affiliation
Department of Neurology, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester, M13 9NQ, UK.Location evidence
Brighton, GB · Author affiliation
Department of Neuroscience, Brighton and Sussex Medical School, University of Brighton and University of Sussex, Brighton, BN1 9PX, UK.Location evidence
Oxford, GB · Author affiliation
Division of Clinical Neurology, Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, Nuffield, University of Oxford, Oxford, OX3 9DU, UK.Location evidence
Tartu, EE · Author affiliation
Department of Neurology and Neurosurgery, Institute of Clinical Medicine, University of Tartu, Tartu 50406, Estonia.Location evidence
Tallinn, EE · Author affiliation
Center of Neurology, East Tallinn Central Hospital, 10138 Tallinn, Estonia.Location evidence
Newcastle upon Tyne, GB · Author affiliation
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4AE, UK.Location evidence
Southampton, GB · Author affiliation
Wessex Neurological Centre, University Hospital Southampton, Southampton, SO16 6YD, UK.Location evidence
Salerno, IT · Author affiliation
Centre for Neurodegenerative Diseases (CEMAND), Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Salerno, Italy.Location evidence
Naples, IT · Author affiliation
IRCCS SYNLAB SDN, 80121 Naples, Italy.Location evidence
Stockholm, SE · Author affiliation
Laboratory of Translational Neuropharmacology, Department of Clinical Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden.Location evidence
Barcelona, ES · Author affiliation
Parkinson's & Movement Disorders Unit; CSUR & ERN-RND for rare movement disorders, Hospital Clínic i Universitari, Barcelona 08036, Catalonia, Spain.Location evidence
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Original abstract
Corticobasal degeneration (CBD) is a late onset progressive neurodegenerative condition of the 4-repeat-tauopathy-type, classically presenting with asymmetrical rigidity, dystonia and myoclonus. In the most recent diagnostic criteria, Armstrong and colleagues (2013) described four clinical phenotypes associated with this pathology, including corticobasal syndrome (CBS), through a large retrospective analysis of published cases and confirmed brain bank cases of CBD. However, predicting CBD pathology remains challenging. With the advent of disease-modifying therapies, it has become particularly important to distinguish Alzheimer's disease pathology from other underlying pathologies. We therefore combined two prospectively recruited cohorts of patients with CBS and analysed their key demographic, clinical and biomarker features. We included a separate cohort from UK brain banks who were diagnosed with CBS in life. We divided patients into three groups: CBS-Alzheimer's (CBS-AD), CBS-non-Alzheimer's (CBS-non-AD) and CBS-indeterminate (CBS-IDT) based on biomarkers and pathology, comparing clinical features, regional volumetric MRI measures and Nucleic Acid-Linked Immuno-Sandwich Assay with detection by next generation sequencing (NULISAseq) blood protein levels between groups. We performed additional analyses of pathologically verified cases. We included 397 participants, of which 57.7% were female. The mean age at symptom onset was 65.9 years. AD biomarkers and pathology permitted classifying 47 (11.8%) of the cases as CBS-AD, 134 (33.8%) as CBS-non-AD and 216 (54.4%) as CBS-IDT. Patients with CBS-AD had a younger age at onset (61.8 years vs 66.1 years, P < 0.01 and less severe motor deficits (non-significantly lower scores on MDS-UPDRS and PSPRS) and more severe cognitive impairment (non-significantly lower scores on MoCA). Patients with CBS-AD had higher rates of cortical sensory impairment (P = 0.087) and lower rates of limb dystonia (P < 0.01) and falls (P < 0.01) compared to the CBS-non-AD group. Volumetric MRI analysis revealed smaller parietal lobe volumes in CBS-AD (P = 0.01). The most common pathological diagnoses were PSP, CBD and AD. Limb dystonia was more common in people with CBD and PSP pathology (P = 0.077). Falls, impaired verbal fluency and impaired vertical saccades were confirmed as more common in PSP (P = 0.046, P = 0.040, P = 0.012, respectively). In summary, younger onset, less parkinsonism and more cognitive and cortical sensory impairment, along with reduced MRI parietal volumes point to CBS-AD, while limb dystonia, falls and worse verbal fluency relate to CBS-non-AD. Clinical, imaging and blood-biomarkers in can augment the Armstrong criteria in predicting the underlying pathology of corticobasal syndromes.